1. Field of the Invention
The invention relates to the synthetic heterovesicular lipid vesicles or liposomes, processes for their manufacture and encapsulation of various materials therein, and treatment of patients with them.
2. Description of Related Art
Multivesicular liposomes are one of the three main types of liposomes, first made by Kim, et al. (Biochim, Biophys. Acta, 782:339-348, 1983), and are uniquely different from the unilamellar (Huang, Biochemistry, 8:344-352, 1969; Kim, et al., Biochim. Biophys. Acta, 646:1-10, 1981) and multilamellar (Bangham, et al., J. Mol, Bio., 13:238-252, 1965) liposomes in that there are multiple non-concentric aqueous chambers within. Previously described techniques for producing liposomes relate to the production of non-multivesicular liposomes; for example, U.S. Pat. Nos. 4,522,803--Lenk, 4,310,506--Baldeschwieler, 4,235,871--Papahadjopoulos, 4,224,179--4,078,052--Papahadjopoulos, 4,394,372--Taylor, 4,308,166--Marchetti, 4,485,054--Mezei, and 4,508,703--Redziniak. For a comprehensive review of various methods of liposome preparation, refer to Szoka, et al. (Ann. Rev. Biophys. Bioeng., 9:467-508, 1980).
Heterovesicular liposomes are lipid vesicles or liposomes characterized by multiple internal aqueous chambers. The lipid vesicles or liposomes with multiple internal aqueous chambers include, but are not limited to, multilamellar lipsomes, stable paucilamellar lipsomes and multivesicular lipsomes wherein the aqueous chambers are non-concentric. It is highly advantageous to provide a liposome delivery system in which two or more different substances are each encapsulated in separate compartments of a single liposome rather than encapsulated together in each compartment of the liposome.